High cortisol response to adrenocorticotrophic hormone identifies ewes with reduced melanocortin signalling and increased propensity to obesity

We have identified female sheep that have either high (HR) or low (LR) cortisol responses to adrenocorticotropin. On a high energy diet, HR have greater propensity to weight gain and obesity, but the underlying mechanisms remain to be fully elucidated. Hypothalamic appetite-regulating peptides (ARP) exert reciprocal effects on food intake and energy expenditure. We aimed to quantify expression and function of ARP in LR and HR ewes (n=4/group). Gene expression for neuropeptide Y (NPY), agouti-related peptide (AgRP) proopiomelanocortin (POMC), melanin-concentrating hormone (MCH), orexin and the melanocortin receptors (MC3R and MC4R) was measured by in situ hybridization. Expression of NPY, AGRP and POMC was similar in HR and LR, but expression of orexin, MCH, MC3R and MC4R was higher (P